New and general strategies for the enantiospecific construction of molecules of medicinal interest (antivirals, antibiotics, antitumor agents, etc ) are important to the overall mission of the NIH. Described within this proposal are the design and development of easily-prepared, enantiomerically-pure molybdenum pi-complexes of unsaturated oxygen and nitrogen hetero- cycles (2H-pyran, 1,2-dihydropyridine, and others) to which a rich variety of substituents can be sequentially and easily attached in a regio-and stereocontrolled fashion. Demetallation after attachment of multiple substituents would provide enantiomerically-pure, substituted oxygen and nitrogen heterocycles. In principle, these pi-complexes function as enantiomerically-pure scaffolds for the rapid assembly of substituted heterocyclic systems of known or potential medicinal value. Therefore, successful achievement of this new strategy would introduce a novel method for the synthesis of important classes of heterocyclic organic compounds with demonstrated biological activity in a wide variety of assays (antiviral, antibiotic, etc). Also, within the context of this grant, a metal binding ligand will be attached to a polymer matrix and to that ligand enantiomerically-pure oxygen and nitrogen heterocyclic scaffolds will be attached. Protocols for the functionalization and demetallation of these polymer-bound enantiomerically-pure heterocyclic scaffolds will be explored. This 'enantiomerically-pure scaffold' strategy, if developed to its fullest potential, could hold great promise for rapid structure-activity- relationship studies of enantiomerically-pure substituted oxygen-and nitrogen heterocyclic systems using combinatorial robotics techniques.